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Increased serum ferritin (SF) is common in hematologic malignancies; however, its prognostic role in acute myeloid leukemia (AML) is not clearly established. We examined the impact of baseline SF on long-term survival in 137 intensively treated AML patients. Patients and baseline characteristics were retrieved from an AML database at Charité University Medical Center Berlin, Campus Virchow Clinic. After c-reactive protein (CRP)-based adjustment for inflammation, patients were grouped according to their baseline SF level. Survival analysis was performed accordingly. A significant decline in overall survival and relapse-free survival was observed in patients with high SF as compared to those with low SF. Furthermore, elevated baseline SF remained an independent poor prognostic factor within the multivariate analysis and was associated with a significant higher risk of relapse and non-relapse mortality (NRM). In conclusion, our data show that elevated baseline SF has a negative impact on long-term survival in intensively treated AML patients.

We describe a consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. Genome-wide linkage analysis identified a 5.8 Mb interval on chromosome 8q with shared homozygosity among the affected persons. Sequencing of genes contained in the interval revealed a homozygous mutation, S100P, in carbonic anhydrase related protein 8 (CA8), which is highly expressed in cerebellar Purkinje cells and influences inositol triphosphate (ITP) binding to its receptor ITPR1 on the endoplasmatic reticulum and thereby modulates calcium signaling. We demonstrate that the mutation S100P is associated with proteasome-mediated degradation, and thus presumably represents a null mutation comparable to the Ca8 mutation underlying the previously described waddles mouse, which exhibits ataxia and appendicular dystonia. CA8 thus represents the third locus that has been associated with quadrupedal gait in humans, in addition to the VLDLR locus and a locus at chromosome 17p. Our findings underline the importance of ITP-mediated signaling in cerebellar function and provide suggestive evidence that congenital ataxia paired with cerebral dysfunction may, together with unknown contextual factors during development, predispose to quadrupedal gait in humans., Competing Interests: The authors have declared that no competing interests exist.

This study was planned to evaluate the feasibility of using the assay of leukocyte arylsulfatase-A (AS-A) activity as a non-invasive diagnostic tool in patients with benign and malignant breast disease. The leukocyte AS-A activity of a total of 81 women was analyzed, including 28 healthy women, 29 women with benign breast disease (BBD) and 24 patients with primary breast cancer (BC). The mean leukocyte AS-A activity in patients with BBD was slightly higher (14.3%) that observed in the healthy subjects, but the difference was not statistically significant. In patients with BC the enzyme activity was significantly higher than in the healthy subjects (60.3%, P<0.05) and in the benign group (40.2%, P<0.05). In addition, since no significant differences have been observed between premenopausal patients and their controls, it is suggested that the measurement of leukocyte AS-A activity may not be a reliable test for differential diagnosis of benign and malignant proliferation in mammary glands due to the possible interfering effect of gonadal hormones on AS-A activity. In contrast, since peri- and postmenopausal BC patients have negligible or no gonadal activity function, the elevation in the activity of leukocyte AS-A in these age groups of patients may only be expected to originate from malignant proliferation. Based on our results, it is concluded that in patients in whom high leukocyte AS-A activities were observed the possibility of the presence of malignancy might also be high. Therefore, this test might be valuable as a non-invasive biochemical technique in combination with other established markers for the identification of masses in the breast.